Scientists at USC untangle the mysteries of cellular reprogramming- a method that could be used to treat diseases

Dr. Justin Ichida, Assistant Professor at USC and lead author of the study

Scientists have long tried to repurpose cells in order to potentially treat various types of conditions. This process, called reprogramming, involves changing one type of cell into another, such as a blood cell into a muscle cell or nerve cell. Although the technique has been around for decades, it has only been effective 1% of the time.

Fortunately, thanks in part to a CIRM grant, Dr. Justin Ichida and other researchers at USC have been able to untangle this complicated process to ensure reprogramming happens more efficiently. The researchers were able to figure out a process that reprograms cells much more reliably than previous methods.

USC scientists have found a solution to untangle twisty DNA, removing kinks so the molecules can be used to reprogram cells to advance regenerative medicine to treat disease.
Photo courtesy of Illustration/iStock

The technique the scientists developed uses an enzyme to untangle reprogramming DNA, similar to how a hairdresser conditions untangled hair. Since DNA molecules are twisty by nature, due to the double helix configuration, they do not respond well when manipulated to change itself. Therefore, reprogramming DNA requires uncoiling, yet when scientists begin to unravel the molecules, they knot up tighter.

“Think of it as a phone cord, which is coily to begin with, then gets more coils and knots when something is trying to harm it,” Dr. Ichida said in a press release by USC.

To smooth the kinks, the researchers treated cells with a chemical and genetic cocktail that activates enzymes that open up the DNA molecules. This process releases the coiled tension and lays out the DNA smoothly, leading to more efficient cellular reprogramming.

This new technique works almost 100% of the time and has been proven in human and mouse cells. The increased efficiency of this techniques opens the possibilities for studying disease development and drug treatments. New cells could be created to replace lost cells or acquire cells that can’t be extracted from people, a problem observed in Parkinson’s, ALS, and other neurological diseases.

Moreover, since these reprogrammed cells are the same age as the parent cell, they could be used to better understand age-related diseases. It is possible that the reprogrammed cells may be better at creating age-accurate models of human disease, which are useful to study a wide array of degenerative diseases and accelerated aging syndromes.

To summarize his work, Dr. Ichida states in the USC press release that,

“A modern approach for disease studies and regenerative medicine is to induce cells to switch their identity. This is called reprogramming, and it enables the attainment of inaccessible tissue types from diseased patients for examination, as well as the potential restoration of lost tissue. However, reprogramming is extremely inefficient, limiting its utility. In this study, we’ve identified the roadblock that prevents cells from switching their identity. It turns out to be tangles on the DNA within cells that form during the reprogramming process. By activating enzymes that untangle the DNA, we enable near 100% reprogramming efficiency.”

The full findings of this study can be found in Cell Stem Cell.

CIRM board member Lauren Miller Rogen appointed to California Alzheimer’s Task Force

Lauren Miller Rogen, Hilarity for Charity co-founder and CIRM Board Member

California has the largest aging population in the United States. The U.S. Census Bureau has estimated that one in five Californians will be 65 or older by the year 2030. Unfortunately with age comes a wide of health related issues that can arise such as Alzheimer’s.

Alzheimer’s is caused by changes in the brain that affect memory and thinking skills. The disease can progress to the point where carrying out the simplest tasks become quite a challenge. In the United States alone, 5.8 million people are living with Alzheimer’s, 630,000 of whom live in California. By 2050, the number of people with Alzheimer’s in the United States is expected to increase to almost 14 million.

To address this growing problem, California Governor Gavin Newsom announced the creation of a California Alzheimer’s Task Force comprised of scientists, politicians, and other individuals dedicated to addressing the needs of the Alzheimer’s community and the impact the disease has on California. The new task force has been tasked with releasing a report on the disease and ways to address the challenges it poses by 2020.

One of these task force members is our very own Lauren Miller Rogen, who is a dedicated member of our governing Board and the co-founder of Hilarity for Charity, a charity organization that raises awareness about and funds for research into Alzheimer’s. In addition to her advocacy work, Lauren is also a screenwriter and actress, staring alongside her husband Seth Rogen in movies such as 50/50 and Superbad.

“I’m so honored to join the Task Force to fight for the 670,000 Californians currently living with Alzheimer’s and for those who care for them,” Miller Rogen said. “This is a tremendous and diverse group who intend to create and propose real ideas to change the course of this disease.”

For Lauren, her journey towards becoming an advocate for Alzheimer’s is a very personal one. Her grandfather died of Alzheimer’s when she was just 12 years old and her grandmother died of the disease six years after that. Now, her mother is struggling with Alzheimer’s, having been diagnosed at the age of 55.

You can read more about Lauren’s story on a previous blog post.

CIRM have given awards totaling over $56 million throughout the years dedicated towards Alzheimer’s related research.

Time and money and advancing stem cell research

The human genome

Way back in the 1990’s scientists were hard at work decoding the human genome, trying to map and understand all the genes that make up people. At the time there was a sense of hope, a feeling that once we had decoded the genome, we’d have cures for all sorts of things by next Thursday. It didn’t quite turn out that way.

The same was true for stem cell research. In the early days there was a strong feeling that this was going to quite quickly produce new treatments and cures for diseases ranging from Parkinson’s and Alzheimer’s to heart disease and stroke. Although we have made tremendous strides we are still not where we hoped we’d be.

It’s a tough lesson to learn, but an important one: good scientific research moves at its own pace and pays little heed to our hopes or desires. It takes time, often a long time, and money, usually a lot of money, to develop new treatments for deadly diseases and disorders.

Many people, particularly those battling deadly diseases who are running out of time, are frustrated at the slow pace of stem cell research, at the years and years of work that it takes to get even the most promising therapy into a clinical trial where it can be tested in people. That’s understandable. If your life is on the line, it’s difficult to be told that you have to be patient. Time is a luxury many patients don’t have.

But that caution is necessary. The last thing we want to do is rush to test something in people that isn’t ready. And stem cells are a whole new way of treating disease, using cells that may stay in the body for years, so we really need to be sure we have done everything we can to ensure they are safe before delivering them to people.

The field of gene therapy was set back years after one young patient, Jesse Gelsinger, died as a result of an early experimental treatment. We don’t want the same to happen to stem cell research.

And yet progress is being made, albeit not as quickly as any of us would like. At the end of the first ten years of CIRM’s existence we had ten projects that we supported that were either in, or applying to be in, a clinical trial sanctioned by the US Food and Drug Administration (FDA). Five years later that number is 56.

Most of those are in Phase 1 or 2 clinical trials which means they are still trying to show they are both safe and effective enough to be made available to a wider group of people. However, some of our projects are in Phase 3, the last step before, hopefully, being given FDA approval to be made more widely available and – just as important – to be covered by insurance.

Other CIRM-funded projects have been given Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA, a new program that allows projects that show they are safe and benefit patients in early stage clinical trials, to apply for priority review, meaning they could get approved faster than normal. Out of 40 RMAT designations awarded so far, six are for CIRM projects.

We are working hard to live up to our mission statement of accelerating stem cell treatments to patients with unmet medical needs. We have been fortunate in having $3 billion to spend on advancing this research in California; an amount no other US state, indeed few other countries, have been able to match. Yet even that amount is tiny compared to the impact that many of these diseases have. For example, the economic cost of treating diabetes in the US is a staggering $327 billion a year.

The simple truth is that unless we, as a nation, invest much more in scientific research, we are not going to be able to develop cures and new, more effective, treatments for a wide range of diseases.

Time and money are always going to be challenging when it comes to advancing stem cell research and bringing treatments to patients. With greater knowledge and understanding of stem cells and how best to use them we can speed up the timeline. But without money none of that can happen.

Our blog is just one of many covering the topic of “What are the hurdles impacting patient access to cell and gene therapies as part of Signal’s fourth annual blog carnival.

CIRM-Funded Researchers Develop Chimeric “Mighty Mouse” Model to Study Alzheimer’s Disease

Dr. Mathew Blurton-Jones, leader of team that developed the chimeric “Mighty Mouse” model at the University of California, Irvine

In ancient Greek mythology, a Chimera was a creature that was usually depicted as a lion with an additional goat head and a serpent for a tail. Due to the Chimera’s animal hybrid nature, the term “chimeric” came to fruition in the scientific community as a way to describe an organism containing two or more different sets of DNA.

A CIRM-funded study conducted by Dr. Mathew Blurton-Jones and his team at UC Irvine describes a way for human brain immune cells, known as microglia, to grow and function inside mice. Since the mice contain a both human cells and their own mice cells, they are described as being chimeric.

In order to develop this chimeric “mighty mouse” model, Dr. Blurton-Jones and his team generated induced pluripotent stem cells (iPSCs), which have the ability to turn into any kind of cell, from cell samples donated by adult patients. For this study, the researchers converted iPSCs into microglia, a type of immune cell found in the brain, and implanted them into genetically modified mice. After a few months, they found that the implanted cells successfully integrated inside the brains of the mice.

By finding a way to look at human microglia grow and function in real time in an animal model, scientists can further analyze crucial mechanisms contributing to neurological conditions such as Alzheimer’s, Parkinson’s, traumatic brain injury, and stroke.

For this particular study, Dr. Blurton-Jones and his team looked at human microglia in the mouse brain in relation to Alzheimer’s, which could hold clues to better understand and treat the disease. The team did this by introducing amyloid plaques, protein fragments in the brain that accumulate in people with Alzheimer’s, and evaluating how the human microglia responded. They found that the human microglia migrated toward the amyloid plaques and surrounding them, which is what is observed in Alzheimer’s patients.

In a press release, Dr. Blurton-Jones expressed the importance of studying microglia by stating that,

“Microglia are now seen as having a crucial role in the development and progression of Alzheimer’s. The functions of our cells are influenced by which genes are turned on or off. Recent research has identified over 40 different genes with links to Alzheimer’s and the majority of these are switched on in microglia. However, so far we’ve only been able to study human microglia at the end stage of Alzheimer’s in post-mortem tissues or in petri dishes.”

Furthermore, Dr. Blurton-Jones highlighted the importance of looking at human microglia in particular by saying that,

“The human microglia also showed significant genetic differences from the rodent version in their response to the plaques, demonstrating how important it is to study the human form of these cell.”

The full results of this study were published in Cell.

Advancing stem cell research in many ways

Speakers at the Alpha Stem Cell Clinics Network Symposium: Photo by Marco Sanchez

From Day One CIRM’s goal has been to advance stem cell research in California. We don’t do that just by funding the most promising research -though the 51 clinical trials we have funded to date clearly shows we do that rather well – but also by trying to bring the best minds in the field together to overcome problems.

Over the years we have held conferences, workshops and symposiums on everything from Parkinson’s disease, cerebral palsy and tissue engineering. Each one attracted the key players and stakeholders in the field, brainstorming ideas to get past obstacles and to explore new ways of developing therapies. It’s an attempt to get scientists, who would normally be rivals or competitors, to collaborate and partner together in finding the best way forward.

It’s not easy to do, and the results are not always obvious right away, but it is essential if we hope to live up to our mission of accelerating stem cell therapies to patients with unmet medical needs.

For example. This past week we helped organize two big events and were participants in another.

The first event we pulled together, in partnership with Cedars-Sinai Medical Center, was a workshop called “Brainstorm Neurodegeneration”. It brought together leaders in stem cell research, genomics, big data, patient advocacy and the Food and Drug Administration (FDA) to tackle some of the issues that have hampered progress in finding treatments for things like Parkinson’s, Alzheimer’s, ALS and Huntington’s disease.

We rather ambitiously subtitled the workshop “a cutting-edge meeting to disrupt the field” and while the two days of discussions didn’t resolve all the problems facing us it did produce some fascinating ideas and some tantalizing glimpses at ways to advance the field.

Alpha Stem Cell Clinics Network Symposium: Photo by Marco Sanchez

Two days later we partnered with UC San Francisco to host the Fourth Annual CIRM Alpha Stem Cell Clinics Network Symposium. This brought together the scientists who develop therapies, the doctors and nurses who deliver them, and the patients who are in need of them. The theme was “The Past, Present & Future of Regenerative Medicine” and included both a look at the initial discoveries in gene therapy that led us to where we are now as well as a look to the future when cellular therapies, we believe, will become a routine option for patients. 

Bringing these different groups together is important for us. We feel each has a key role to play in moving these projects and out of the lab and into clinical trials and that it is only by working together that they can succeed in producing the treatments and cures patients so desperately need.

Cierra Jackson: Photo by Marco Sanchez

As always it was the patients who surprised us. One, Cierra Danielle Jackson, talked about what it was like to be cured of her sickle cell disease. I think it’s fair to say that most in the audience expected Cierra to talk about her delight at no longer having the crippling and life-threatening condition. And she did. But she also talked about how hard it was adjusting to this new reality.

Cierra said sickle cell disease had been a part of her life for all her life, it shaped her daily life and her relationships with her family and many others. So, to suddenly have that no longer be a part of her caused a kind of identity crisis. Who was she now that she was no longer someone with sickle cell disease?

She talked about how people with most diseases were normal before they got sick, and will be normal after they are cured. But for people with sickle cell, being sick is all they have known. That was their normal. And now they have to adjust to a new normal.

It was a powerful reminder to everyone that in developing new treatments we have to consider the whole person, their psychological and emotional sides as well as the physical.

CIRM’s Dr. Maria Millan (right) at a panel presentation at the Stanford Drug Discovery Symposium. Panel from left to right are: James Doroshow, NCI; Sandy Weill, former CEO Citigroup; Allan Jones, CEO Allen Institute

And so on to the third event we were part of, the Stanford Drug Discovery Symposium. This was a high level, invitation-only scientific meeting that included some heavy hitters – such as Nobel Prize winners Paul Berg and  Randy Schekman, former FDA Commissioner Robert Califf. Over the course of two days they examined the role that philanthropy plays in advancing research, the increasingly important role of immunotherapy in battling diseases like cancer and how tools such as artificial intelligence and big data are shaping the future.

CIRM’s President and CEO, Dr. Maria Millan, was one of those invited to speak and she talked about how California’s investment in stem cell research is delivering Something Better than Hope – which by a happy coincidence is the title of our 2018 Annual Report. She highlighted some of the 51 clinical trials we have funded, and the lives that have been changed and saved by this research.

The presentations at these conferences and workshops are important, but so too are the conversations that happen outside the auditorium, over lunch or at coffee. Many great collaborations have happened when scientists get a chance to share ideas, or when researchers talk to patients about their ideas for a successful clinical trial.

It’s amazing what happens when you bring people together who might otherwise never have met. The ideas they come up with can change the world.

Media shine a spotlight on dodgy stem cell clinics

A doctor collects fat from a patient’’s back as part of an experimental stem cell procedure in Beverly Hills, Calif. on Dec. 5, 2014. (Raquel Maria Dillon / Associated Press)

For several years now, we have been trying to raise awareness about the risks posed by clinics offering unproven or unapproved stem cell therapies. At times it felt as if we were yelling into the wind, that few people were listening. But that’s slowly changing. A growing number of TV stations and newspapers are picking up the message and warning their readers and viewers. It’s a warning that is getting national exposure.

Why are we concerned about these clinics? Well, they claim their therapies, which usually involve the patient’s own fat or blood cells, can cure everything from arthritis to Alzheimer’s. However, they offer no scientific proof, have no studies to back up their claims and charge patients thousands, sometimes tens of thousands of dollars.

In the LA Times, for example, reporter Usha Lee McFarling, wrote an article headline “California has gone crazy for sketchy stem cell treatments”. In it she writes about the claims made by these clinics and the dangers they pose:

“If it sounds too good to be true, it is. There is no good scientific evidence the pricey treatments work, and there is growing evidence that some are dangerous, causing blindness, tumors and paralysis. Medical associations, the federal government and even Consumer Reports have all issued stern warnings to patients about the clinics.”

In Denver, the ABC TV station recently did an in-depth interview with a local doctor who is trying to get Colorado state legislators to take legal action against stem cell clinics making these kinds of unsupported claims.

Chris Centeno of the Centeno-Schultz Clinic, who’s specialized in regenerative medicine and research for more than a decade, said too many people are simply being scammed.

“It’s really out of control,” he told the station.

ABC7 did a series of reports last year on the problem and that may be prompting this push for a law warning consumers about the dangers posed by these unregulated treatments which are advertised heavily online, on TV and in print.

In California there is already one law on the books attempting to warn consumers about these clinics. CIRM worked with State Senator Ed Hernandez to get that passed (you can read about that here) and we are continuing to support even stronger measures.

And the NBC TV station in San Diego recently reported on the rise of stem cell clinics around the US, a story that was picked up by the networks and run on the NBC Today Show.

One of the critical elements in helping raise awareness about the issue has been the work done by Paul Knoepfler and Leigh Turner in identifying how many of these clinics there are around the US. Their report, published in the journal Cell Stem Cell, was the first to show how big the problem is. It attracted national attention and triggered many of the reports that followed.

It is clear momentum is building and we hope to build on that even further. Obviously, the best solution would be to have the Food and Drug Administration (FDA) crack down on these clinics, and in some cases they have. But the FDA lacks the manpower to tackle all of them.

That’s where the role of the media is so important. By doing stories like these and raising awareness about the risks these clinics pose they can hopefully help many patients avoid treatments that will do little except make a dent in their pocket.

The Sad Lane: How I navigated one of the happiest times of my life while my mom was losing hers to Alzheimer’s

In 1983 President Ronald Reagan named November as Alzheimer’s Awareness month, to raise awareness about the growing impact the disease was having on Americans. At the time there were less than two million people with the disease. Today that number has grown to more than five million and is expected to reach 16 million by the year 2050. There is no cure and no effective treatments.

To mark Alzheimer’s Awareness month we are reprinting an article that CIRM Board member and Patient Advocate for Alzheimer’s, Lauren Miller, wrote for Lenny magazine, charting her own personal journey with the disease.

The Sad Lane

Stem Cell Roundup: Clinical Trial on the Horizon for Parkinson’s Disease, New Probe Targets Tricky Cancer Cells – Rare Brain Disease May Be Key to Alzheimer’s Insights

Stem Cell Image of the Week: This week’s image shows dopamine producing brain cells. These are the cells that are depleted in people with Parkinson’s Disease.

Unknown

Photo courtesy of B. Bick, . Poindexter, UT Med. School/SPL

Parkinson’s disease news: a new clinical trial, a new face of the disease  (Kevin McCormack)

In his long and illustrious career Alan Alda has worn many hats. First as the star of the hit TV show “M*A*S*H” (the season finale of that is still the most watched TV show ever), then as a writer, director and movie star and, more recently, as the face of popular science and science communications. This week Alda revealed that he has Parkinson’s disease (PD).

In a post on Twitter he said:

“I have decided to let people know I have Parkinson’s to encourage others to take action. I was Diagnosed 3 and a half years ago, but my life is full. I act, I give talks, I do my podcast, which I love. If you get a diagnosis, keep moving!”

CIRM Board member David Higgins echoed those sentiments in an interview on KUSI TV News, San Diego. Dr. Higgins is the patient advocate member for Parkinson’s on the Board, and was diagnosed with PD in 2011, he says being active physically and intellectually are important in helping cope with PD and leading a normal life.

There was also some encouraging news about PD on the research front. Scientists in Japan are about to start a clinical trial using iPSCs to treat people with PD. The cells are created by taking blood stem cells from healthy donors and turning them into dopaminergic progenitors, precursors to the kind of cell destroyed by PD. The cells will then be transplanted into the brains of seven patients with PD.

The researchers, from Kyoto University, say previous studies show the cells could survive in monkeys for up to two years and help improve symptoms of Parkinson’s disease in the primates.

New Molecular Probe Targets Elusive Cancer Stem Cells in Mice (Adonica Shaw)

180802 cancer cells

A group of researchers at the University of Illinois made an advance in how we treat cancer patients this week. In a paper, published in the journal ACS Central Science, the researchers described a new and more effective way of identifying cancer stem cells in cultures of multiple human cancer cell lines as well as in live mice.

After a primary tumor is treated, cancer stem cells may still lurk in the body, ready to metastasize and cause a recurrence of the cancer in a form that’s more aggressive and resistant to treatment. The researchers developed a molecular probe that seeks out these elusive cells and lights them up so they can be identified, tracked and studied not only in cell cultures, but in their native environment: the body.

While other commercial agents are available to flag cancer stem cells, their application is limited, Chan said. Some cannot distinguish between live and dead cells, others can mistakenly bind to wrong targets. The most popular – antibodies that seek out markers on the cell’s surface – are specific to cell types and their large size can prevent them from reaching the small spaces where cancer stem cells tend to lurk. All are designed for use in cell cultures or artificial tumor environments, which lack the complexity of the whole body, Chan said.

In contrast, their new probe, called AlDeSense, is a small molecule that binds to an enzyme related to the property of stemness in cancer cells. The probe becomes activated, emitting a fluorescent signal only when it reacts with the target enzyme – which cancer stem cells produce in high concentrations.

In a series of experiments, the group found that the enzyme seems to be a marker of stemness across many types of cancer, indicating that AlDeSense may be broadly applicable for clinical imaging.

The researchers demonstrated that AlDeSense is compatible with two major cellular techniques – flow cytometry and confocal imaging.

The ability to find and track cancer stem cells in the body, as well as their state of stemness – the signal decreases as the cells differentiate – allowed the researchers to follow cells from injection to tumor as they spread through the bodies of the mice, answering some fundamental questions of how cancer stem cells behave.

According to the researchers nobody knew what happens between injection of cancer stem cells and removal of a tumor prior to this study. There are a lot of models that hypothesize about how cancer stem cells differentiate and grow, but limited experimental data exists.

Through their study, they saw the stemness properties are maintained in the population, even after they metastasize. There’s something about the environment in the body that supports stem cell characteristics. With AlDeSense, now they can profile that environment.

Since they know that the probe only interacts with that one target, they can use the probe to look for a drug that can inhibit this enzyme and verify it in cells and in live animals. The group is currently pursuing a screening for inhibitors or drugs that can kill cancer stem cells by targeting this enzyme.

Tackling a Rare Brain Disease May Also Lead to Alzheimer’s Insights (Todd Dubnicoff)

Alzheimer’s disease and ALS are very complex neurodegenerative disorders, making it very difficult for researchers to tease out the underlying causes let alone find treatments. To make inroads into a better understanding of these incurable diseases, scientists at City of Hope decided to first tackle a related, yet relatively more simple, nervous system disorder called Alexander disease. And this week, the strategy paid off with newly published research in Cell Stem Cell, funded in part by CIRM, describing the development of a patient-derived stem cell model system that could help evaluate novel treatments for all of these neurodegenerative diseases.

AlexanderDisease

An Alexander disease patient's stem cell-derived astrocytes (green) inhibits the growth of precursor cells that, in healthy patients, becomes myelin and speed up the brain's communication network. Credit: Yanhong Shi/City of Hope

The team generated astrocytes, a type of nervous system cell, using induced pluripotent stem cells derived from Alexander disease patients. It was previously known that the mutation in Alexander disease causes the patient’s astrocytes to block another cell type’s ability to produce myelin, the protective covering over neurons that’s critical for communication between nerve cells. But it wasn’t clear how this inhibition happened. In this study, the team found a possible culprit, a protein called CHI3L1 that’s secreted by the patient-derived astrocytes (but not by those from healthy individuals) and interferes with myelin production. So, finding drugs that target CHI3L1 could lead to therapies for Alexander disease.

Dysfunctional astrocytes have also been implicated in ALS and Alzheimer’s disease. So, using this newly developed model system for studying astrocytes could lead to new therapeutic strategies. In a press release, team leader Dr. Yanhong Shi, PhD, provides a specific example how this could work:

“The bulk of ApoE4 resides in astrocytes; ApoE4 is a gene variant known for increasing the risk of Alzheimer’s disease. So, if we understand how astrocytes function, then we can develop therapies to treat Alexander disease and perhaps other diseases that involve astrocytes, such as Alzheimer’s and ALS.”

Promising Advances in Alzheimer’s Research Could Create More Advanced Therapy Options

Screen Shot 2018-08-01 at 12.10.55 PM

Photo Courtesy of NIH

New developments in Alzheimer’s research are bringing us closer to more precise therapies for this debilitating disease.

Alzheimer’s disease, is characterized by the formation of amyloid plaques in the brain, which interfere with the normal communication flow between brain cells, leading to debilitating symptoms like memory loss and impaired decision-making. These plaques are made out of beta-amyloid proteins that stick together.

Over the past few years, researchers from several institutions have been working to develop antibodies that bind to and neutralize the toxic effects of the beta-amyloid. The search for effective antibodies, although promising, has been riddled with setbacks. Knowing this, a team of researchers from Brigham and Women’s Hospital in Boston, MA, decided to approach this issue from a different angle – by conducting experiments to identify a better way of targeting beta-amyloid. Their goal was to develop a more efficient antibody to be used in Alzheimer’s therapy.

Principal investigator Dominic Walsh and team came up with a novel technique to collect beta-amyloid and to prepare it in the laboratory.

walsh-400x520

Dominic Walsh, PH.D.

“Many different efforts are currently underway to find treatments for Alzheimer’s disease, and anti-[beta-amyloid] antibodies are currently the furthest advanced,” says Walsh. “But the question remains: what are the most important forms of [beta-amyloid] to target? Our study points to some interesting answers,” the lead researcher adds, and these answers are now reported in an open access paper published in the journal Nature Communications.”

Beta-amyloid can be found in many forms. At one end of the spectrum, it exists as a single protein, or monomer, which isn’t necessarily toxic.

At the other end, there is the beta-amyloid plaque, in which many beta-amyloid proteins become tangled together. Beta-amyloid plaques are large enough to be observed using a traditional microscope, and they are involved in the development of Alzheimer’s.

In the current study, as well as in a previous one, Walsh and team looked at beta-amyloid structures to identify the ones that are most harmful in the brain.

Typically specialists use synthetic beta-amyloid samples to create a laboratory model of Alzheimer’s disease in the brain. Very few scientists actually collect beta-amyloid from the brains of individuals diagnosed with the disease.

In the current study, Walsh and team focused on finding better a more specific antibody to target the toxic forms of beta-amyloid but not the less harmful forms. To do so, they developed a novel screening test that requires extracting beta-amyloid from brain samples from people with Alzheimer’s. They added these extracts to induced pluripotent stem cell-derived human neurons and observed the ability of the different antibodies to block the toxic effects of the beta-amyloid.

This screening test allowed the team to discover a particular antibody — called “1C22” — that is able to block toxic forms of beta-amyloid more effectively than other antibodies currently being tested in clinical trials.

Walsh explained the implications of their novel screening method:

“We anticipate that this primary screening technique will be useful in the search to identify more potent anti-[beta-amyloid] therapeutics in the future.”

Using laughter to help find a treatment for Alzheimer’s

Alzheimer's

In 1983, when President Ronald Reagan designated an annual National Alzheimer’s Disease Awareness Month fewer than two million Americans had Alzheimer’s. Today, that number is close to 5.5 million and estimates suggest it will rise to 16 million by 2050. There are no treatments. No cure. But around the globe people are working hard to change that.

At CIRM we have invested more than $60 million in 21 projects aimed at developing a deeper understanding of the disease and, we hope, one day developing effective treatments.

d03a2-lauren-miller-premiere-50-50-01

Lauren Miller Rogen

One of those helping lead that fight is our Board member Lauren Miller Rogen. Lauren has a family history of the disease and uses that to fuel her activism not just on our Board but through Hilarity for Charity, the organization she co-founded with her husband, Seth Rogen.

Lauren was recently profiled by the stem cell advocacy group Americans for Cures, talking about the impact the disease has had on her family, her advocacy on behalf of families struggling to cope with the disease and why she feels humor is such a powerful tool to raise awareness and hope in the fight against Alzheimer’s.

It’s a great interview and you can read it here.